The proposed research will enable us to find potential pharmacogenomic and clinical predictors of response to acamprosate. Furthermore, this study will guide the functional studies in project #1, which will reveal a possible molecular basis of the therapeutic effect of acamprosate. It will also provide an opportunity to develop synergy with the other projects and create an infrastructure for the future projects focused on identification of the genomic predictors of treatment response to available and novel medications for treatment of alcohol dependency. As the number of medications used for the treatment of alcohol dependency is expected to grow, prediction of the individuals' ability to tolerate and respond to specific medication will be necessary to guide the choice of the right medication for the right person at the right time, which is the main goa/of our Mayo CITA (Center for Individualized Treatment of Alcohol Dependence). If positive associations are found, functional genomic studies can be designed to uncover mechanisms of the therapeutic response to acamprosate. Moreover, this project will create synergy with Projects #1 and #4, thus creating an infrastructure for future pharmacogenomic research, which is an overarching goal of this P20 proposal. Although the initially selected candidate genetic variations will likely uncover only a subset of the predictors of treatment outcome, the proposed study design will be important step towards future use of pharmacogenomic predictors in guidance of choice for pharmacological treatment of alcohol dependency. Selection of the narrowly defined phenotypes reflecting fully developed severe cases of alcoholism, may magnify the effect size and increase the probability of its detection (Schork and Schork, 1998), which is an important advantage of the proposed study. This line of research may help to develop an algorithm for the treatment of alcohol dependence incorporating identification of the genetic variations predicting response to specific medications. This could ultimately lead to reductions in direct care costs through decreased utilization of the medical services and indirect cost savings through increased treatment effectiveness and subsequent improvement in quality of life for patients and families.